The cytokine interleukin-7 (IL-7) has been shown to have a crucial role in the maintenance of homeostasis of the immune system. Much of what is known about IL-7 relates to its role as a survival factor and there has been less focus on the signaling pathways and targets through which IL-7 supports cell cycle entry. To gain a better understanding about the crucial role of IL-7 in the homeostatic proliferation of lymphocytes in immunodeficient hosts and how this pathway may be manipulated to induce immune reconstitution, we will study the mechanisms by which IL-7 promotes survival as well as the nature of the IL-7 proliferative signal that commits cells to cycle. We propose that IL-7 promotes the proliferation and survival of lymphocytes through Cdc25A and current studies are underway to test this hypothesis. These studies will advance our understanding of how the cell cycle is regulated, revealing novel therapeutic approaches for treating diseases, such as cancer, where cell cycling is deregulated. In addition, these findings could initiate the development of new treatments to induce cell proliferation in conditions where there has been excessive cell death as in heart disease and neurodegenerative diseases.